EP1201202A1 - Artificial neural tube - Google Patents

Artificial neural tube Download PDF

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Publication number
EP1201202A1
EP1201202A1 EP00940915A EP00940915A EP1201202A1 EP 1201202 A1 EP1201202 A1 EP 1201202A1 EP 00940915 A EP00940915 A EP 00940915A EP 00940915 A EP00940915 A EP 00940915A EP 1201202 A1 EP1201202 A1 EP 1201202A1
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EP
European Patent Office
Prior art keywords
tube
collagen
nerve
fine fibrous
fibrous collagen
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP00940915A
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German (de)
English (en)
French (fr)
Inventor
Yasuhiko Shimizu
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Tapic International Co Ltd
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Tapic International Co Ltd
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Filing date
Publication date
Application filed by Tapic International Co Ltd filed Critical Tapic International Co Ltd
Publication of EP1201202A1 publication Critical patent/EP1201202A1/en
Withdrawn legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58—Materials at least partially resorbable by the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/04—Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/227—Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/24—Collagen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2210/00—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2210/0004—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof bioabsorbable
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/32—Materials or treatment for tissue regeneration for nerve reconstruction

Definitions

  • the present invention relates to an artificial tube for nerve.
  • a peripheral nerve having a function which is not very important may be partially excised from the same patient, and autotransplantation may be performed to the severed site of the nerve using this peripheral nerve segment.
  • autotransplantation may be performed to the severed site of the nerve using this peripheral nerve segment.
  • the spinal cord is considered to not regenerate once it has been damaged.
  • the spinal cord is damaged due to injury or tumor, the damaged spinal cord does not regenerate, and all function below the damaged portion is lost with paralysis remaining as the sequella.
  • experiments on animals have begun to be conducted that prove that the spinal cord is also able to regenerate.
  • the spinal cord is severed sharply and accurately re-sutured, function is restored and the damaged portion is repaired to a considerable degree.
  • the portion of the spinal cord regenerates and function is at least partially restored.
  • an artificial tube for nerve that induces axons regenerated from severed nerve stumps to extend in the proper direction without pressing on the regenerated nerve following nerve regeneration, and causes rapid restoration of blood flow by promoting infiltration of blood capillaries from the body to promote regeneration of nerve tissue.
  • an artificial tube for spinal cord that connects not only peripheral nerves but also the missing portions of spinal cord, and promotes proper regeneration of spinal cord tissue along with restoration of function.
  • the present invention relates to an artificial tube for nerve which is characterized in that the artificial tube for nerve has fine fibrous collagen bodies (30) in the lumen of a tube (10, 20) comprised of a biodegradable and absorbable material, the voids inside the fine fibrous collagen bodies being filled with laminin.
  • the present invention relates to a method for producing an artificial tube for nerve which is characterized in that the method comprises steps: preparing a tube (10, 20) comprised of a biodegradable and absorbable material, introducing a hydrochloric acid solution of collagen into the lumen of the tube, freezing and then freeze-drying the tube to form fine fibrous collagen bodies (30), performing thermal crosslinking treatment on the tube having the fine fibrous collagen bodies in its lumen, and introducing laminin into the fine fibrous collagen bodies.
  • the length and inner diameter of the tube (10, 20) that composes the artificial tube for nerve of the present invention differ according to the length and thickness of the severed portion of the nerve, in order to cover, for example, a missing portion on the order of about 25 mm of the sciatic nerve (using the example of a cat), the length is about 28-35 mm, and preferably about 30 mm, and the inner diameter is about 1-8 mm, and preferably about 4 mm.
  • the length of the tube is determined according to the length of the severed portion, while the inner diameter is preferably about 2-12 mm and particularly preferably about 10 mm.
  • the tube (10, 20) composed of a material that is biodegradable and absorbable in vivo that composes the artificial tube for nerve of the present invention retains the shape of the tube to prevent invasion of body cells from outside the tube during the time until the severed nerve regenerates and the severed location is rejoined (about 1-3 months). Consequently, despite being biodegradable and absorbable in vivo, it is necessary that the material is able to retain its shape in the body for a certain period of time.
  • base materials of such a material include mesh materials selected from the group consisting of polyglycolic acid, polylactic acid, copolymer of glycolic acid and lactic acid, copolymer of lactic acid and ⁇ -caprolactone, polydioxanone and copolymer of glycolic acid and trimethylene carbonate, a mesh tube comprised of polyglycolic acid is preferable.
  • a tube comprised of fine fibrous collagen can also be used preferably.
  • the artificial tube for nerve of the present invention (hereinafter referred to as "Type 1") in which a tube comprised of a biodegradable and absorbable material has a coating layer (13, 23) comprised of gelatin or collagen on at least the outside of a mesh tube comprised of a material such as polyglycolic acid.
  • the thickness of the tube (referring to the thickness of the tube wall in the form of a cylinder, and to apply similarly hereinafter) is preferably about 0.1-3 mm, and particularly preferably about 0.5-2 mm.
  • the tube obstructs regeneration of body tissue, and if the thickness is less than 0.1 mm, degradation and absorption of the tube proceed too rapidly, and the shape of the tube is not maintained until the nerve finishes regenerating.
  • its thickness should preferably be about 0.2-5 mm, and particularly preferably about 0.5-3 mm.
  • the base material of the above tube is a material such as polyglycolic acid
  • said tube is in the form of a mesh to impart water permeability to the base material which is itself hydrophobic.
  • the mesh pore size of this mesh tube (11) is preferably about 5-30 ⁇ m, and particularly preferably about 10-20 ⁇ m. If the mesh pore size is less than about 5 ⁇ m, cells and tissue are unable to proliferate, while if the mesh pore size exceeds about 30 ⁇ m, entry of tissue becomes excessive.
  • said material itself does not have an action that promotes tissue regeneration, although it is made to have a coating layer (13, 23) comprised of a material having action that promotes tissue regeneration on at least the outside of tube (11) serving as the base material, it is preferably coated or filled with a material having action that promotes tissue regeneration on both the inside and outside of the tube serving as said base material and inside the mesh pores.
  • the thickness of the coating layers (13,23 and/or 12,22) is preferably about 0.2-5 mm, and particularly preferably 0.5-3 mm.
  • examples of such materials that promote tissue regeneration include collagen or gelatin which have water-permeability, do not cause foreign body reactions when applied in the body, have excellent bioaffinity and tissue compatibility, and have an action that promotes tissue regeneration.
  • Collagen originating in various animals conventionally used in the past can be used for the collagen raw material, preferable examples of which include type I collagen or a mixture of type I and type III collagen originating in the skin, bone, cartilage, tendon and organs of cows, pigs, rabbits, sheep, kangaroos or birds that is solubilized by acid, base, enzymes and so forth.
  • the coating layers composed of collagen are layers having an amorphous structure in which collagen molecules are dispersed.
  • Purified gelatin according to the Japanese Pharmacopoeia can be used for the raw material of a coating layer composed of gelatin.
  • the tube base material composed of a material that is biodegradable and absorbable in vivo can be the mesh tube (11) composed of a material such as the above-mentioned polyglycolic acid, or a tube (21) composed of fine fibrous collagen having collagen having an action of promoting tissue regeneration for its raw material.
  • Type 2 the artificial tube for nerve of the present invention
  • the material that is biodegradable and absorbable in vivo is a tube composed of fine fibrous collagen
  • the coating layer (23 and/or 22) possessed on at least the outside of said tube is composed of collagen.
  • This material composed of fine fibrous collagen is a matrix or thread-like woven or knitted product of a non-woven fabric-like multi-element structure in which fine fibers composed of collagen molecules are overlapped in multiple layers (and more specifically, using microfibers having a diameter of 3-7 nm composed of several collagen molecules as the basic unit, said microfibers are bundled to form ultrafine fibers having a diameter of 30-70 nm, said ultrafine fibers are further bundled to form fine fibers having a diameter of 1-3 ⁇ m, rows of bundles of said fine fibers are laminated vertically and horizontally in alternating fashion to form fibers having a diameter of 5-8 ⁇ m, and said fibers are fallen on top of one another in a coaxial direction to form sheet fibers having a diameter of 20-50 ⁇ m, ultimately resulting in the formation a fibrous collagen as the maximum unit by randomly intermingling these sheet fibers 11; see Fig.
  • Tube (21) that uses this for its material has an inner diameter and length similar to tube (11) of the artificial tube for nerve of type 1. Its thickness is preferably about 0.5-5 mm, and particularly preferably 1-2 mm. In addition, in the case of using the artificial tube for nerve of the present invention as an artificial tube for spinal cord, its thickness is preferably about 0.5-5 mm, and particularly preferably about 1-3 mm.
  • the coating layer (23 and/or 22) composed of collagen formed on at least the outside of this tube (21) uses conventional solubilized type I or a mixed collagen of type I and type III of animal origin for its raw material similar to the non-woven fabric-like multi-element structure composed of fine fibrous collagen for the tube base material. However, the form is that of a layer having an amorphous structure in which collagen molecules are dispersed. Furthermore, the thickness of the coating layer is preferably about 0.1-2 mm, and particularly preferably about 0.5-1 mm.
  • the artificial tube for nerve of the present invention has fine fibrous collagen bodies (30) in the lumen of a tube (10,20) composed of a biodegradable and absorbable material, and laminin is filled in the voids in said fine fibrous collagen bodies (here, said fine fibrous collagen bodies have a structure that is substantially similar to the non-woven fabric-like multi-element structure composed of fine fibrous collagen serving as the tube base material; see Fig. 3).
  • nerve fibers use said fine fibrous collagen bodies as footholds for regeneration for the purpose of regenerating and extending.
  • said fine fibrous collagen bodies are gradually digested and destroyed during the course of regeneration and extension of nerve fibers.
  • the tube base material (11 or 21) composed of a material that is biodegradable and absorbable in vivo is a tube (11) composed of a cylindrical mesh body made of polyglycolic acid, and the coating layer (23 and/or 22) of said tube is composed of amorphous collagen.
  • a mesh tube (11) is first produced using a material such as polyglycolic acid.
  • a material such as polyglycolic acid.
  • fibers of polyglycolic acid and so forth fibers having a diameter of, for example, 0.1 mm are woven into the shape of a cylinder to obtain a mesh tube having the above thickness.
  • the prepared mesh tube (11) is then coated with the above collagen or gelatin solution or immersed in said solution (this coating or immersion is to be hereinafter referred to as "Coating") and then air-dried to form a collagen or gelatin coating layer (13,23 and/or 12,22) on at least the outside of mesh tube (11) and inside the mesh pores (in the case of forming said collagen or gelatin coating layer only on the outside of said mesh tube and inside the mesh pores, a rod made of Teflon and so forth that makes contact with the inside of said mesh tube should be inserted into the lumen of said mesh tube prior to coating of said collagen or gelatin solution).
  • an approximately 1 N hydrochloric acid solution (pH of about 3) preferably containing about 1-3 wt%, and particularly preferably about 1-2 wt%, of collagen, or preferably an about 2-30 wt%, and particularly preferably about 10-20 wt%, aqueous gelatin solution is used.
  • mesh tube (11) it is convenient to coat mesh tube (11) with collagen or gelatin after treating with plasma discharge, ozone emission or other hydrophilization treatment to impart mesh tube (11) with hydrophilic properties.
  • the rod having a diameter of preferably about 2-12 mm, and particularly preferably about 10 mm is used.
  • the core is immersed in an approximately 1 N hydrochloric acid solution containing preferably about 0.5-3 wt%, and particularly preferably about 1-2 wt%, of collagen, and a collagen hydrochloric acid solution layer having a thickness of preferably about 5-20 mm, and particularly preferably about 10 mm, is formed on the surface of said core followed by freezing (for example, at about 0°C for about 12 hours).
  • a collagen hydrochloric acid solution layer is formed having a thickness of preferably about 5-30 mm, and particularly preferably about 20 mm, followed by freezing.
  • this fine fibrous collagen layer is placed in a pouch made of polyethylene and so forth, sealed and degassed or not degassed followed by mechanical pressing of said fine fibrous collagen layer to compress the collagen layer.
  • This compression procedure is performed such that the thickness of said fine fibrous collagen layer after compression is preferably about 0.5-5 mm, and particularly preferably about 1-2 mm, or in the case of using as an artificial tube for spinal cord, the compression procedure is performed such that the thickness of the fine fibrous collagen layer after compression is preferably about 0.5-5 mm, and particularly preferably about 1-3 mm.
  • wet spinning is performed to first produce a collagen thread-like product from the above collagen hydrochloric acid solution after which this is woven or knitted into the shape of a tube.
  • the remainder of the procedure starting with freezing is the same as that described above.
  • Collagen coating layer (23 and/or 22) is further formed on at least the outside of compressed fine fibrous collagen layer (21) formed in this manner. As a result of forming these collagen coating layers (23 and/or 22), a tube (20) composed of a biodegradable and absorbable material is obtained having even greater strength.
  • the tube composed of fine fibrous collagen layer (21) removed from the above-mentioned rod or core is preferably again coated with or immersed in an approximately 1 N hydrochloric acid solution containing preferably about 0.5-3 wt%, and particularly preferably about 1-2 wt%, collagen, and a collagen hydrochloric acid solution layer is formed on at least the outside of fine fibrous collagen layer (21) followed by air-drying.
  • This coating or immersion and air-drying procedure is repeated several times, and preferably 5-20 times, to obtain a collagen coating layer (23 and/or 22) having an amorphous structure in which collagen molecules are dispersed (the thickness of the collagen hydrochloric acid solution layer is preferably about 0.2-1.0 mm, and particularly preferably about 0.5 mm, overall).
  • the thickness is the same.
  • Tube (20) prepared in this manner can be handled easily and allows easy suturing with nerves due to its high tear strength as compared with a tube consisting of compressed fine fibrous collagen layer (21) alone (due to partial entry of amorphous collagen into said compressed fine fibrous collagen layer and partial dissolution and precipitation of collagen at the interface of said compressed fine fibrous collagen layer and said collagen coating layer).
  • Fine fibrous collagen bodies (30) are formed in the lumen of tube (10,20) composed of a biodegradable and absorbable material prepared as described above. Formation of these fine fibrous collagen bodies (30) should be performed in the same manner as formation of the tube (21) of type 2 with the exception of not performing the core filling and compression procedure. In other words, the above collagen hydrochloric acid solution is poured into the lumen of these tubes using tube (10) or tube (20) as a kind of mold followed by freezing and freeze-drying.
  • crosslinking treatment is performed in order to impart resistance to water-solubility to tube (21) composed of the collagen or gelatin coating layer (13,23 and/or 12,22) and compressed fine fibrous collagen (in the case of type 2, this crosslinking treatment may also be performed after preparing tube (21) and before formation of the coating layer (23 and/or 22).
  • Crosslinking treatment is advantageous for the artificial tube for nerve of the present invention because it maintains the shape of the tube and prevents invasion of cells from outside the artificial tube for nerve during the time until the peripheral nerve is finished regenerating.
  • crosslinking treatment is performed to an extent that the shape of the tube is retained for 1-3 months after application in the body.
  • examples of crosslinking methods include gamma ray crosslinking, ultraviolet ray crosslinking, electron beam crosslinking, thermal dehydration crosslinking, glutaraldehyde crosslinking, epoxy crosslinking and water-soluble carbodiimide crosslinking, thermal dehydration crosslinking is preferable because it is easy to control the degree of crosslinking and does not have an effect on the body even when used for crosslinking treatment.
  • the crosslinking treatment is performed in a vacuum at a temperature of, for example, about 105-150°C, preferably about 120-150°C, and particularly preferably about 140°C, for, for example, about 6-24 hours, preferably about 6-12 hours, and particularly preferably about 12 hours.
  • a component that aids the growth of nerve fibers is filled into the voids in the above fine fibrous collagen bodies (30).
  • a component that aids the growth of nerve fibers is filled into the voids in the above fine fibrous collagen bodies (30).
  • a component that aids the growth of nerve fibers is filled into the voids in the above fine fibrous collagen bodies (30).
  • a component include laminin, and particularly preferably human laminin.
  • tube (10,20) having fine fibrous collagen bodies (30) in its lumen is immersed in a solution of laminin dissolved in PBS (Phosphate Buffered Saline), or a PBS solution of laminin is injected into said fine fibrous collagen bodies.
  • crosslinking treatment and preferably thermal dehydration crosslinking treatment, is preferably performed on the said fine fibrous collagen bodies produced for the same reasons as in the production step of fine fibrous collagen bodies (30).
  • an additional component for promoting regeneration and extension of nerve fibers such as at least one among cell nutrient/growth factors like TGF- ⁇ , inflammatory cells including autologous macrophages (cultured in vitro) and autologous, homologous or heterologous myelin (medullary sheath) forming cells such as oligodendroglia and Schwann cells, are preferably introduced into said fine fibrous collagen bodies in addition to this laminin filling. Introduction of these additional components should be carried out in accordance with routine methods.
  • the entire structure is air-dried to complete production of the artificial tube for nerve of the present invention (naturally, this does not mean that procedures required for distribution on the market, such as packaging and sterilization, do not have to be carried out).
  • the artificial tube for nerve prepared in the manner described above can be used to restore nerve function by inserting both stumps of a nerve that has been severed by injury or surgical procedure into the present artificial tube for nerve and fixing those portions by knotting suture to induce axon regeneration and extension in the proper direction, and allow axons to reach from the peripheral nerve trunk to a neuromuscular junction or peripheral sensory receptor.
  • the spinal cord is damaged due to injury as well, by removing the vertebrae corresponding to the damaged portion and covering the damaged portion of the spinal cord with the present artificial tube for nerve, it is believed that the damaged spinal cord can be regenerated and its function restored.
  • Polyglycolic acid (PGA) fibers (diameter: 0.1 mm) were woven into a tubular shape to prepare a polyglycolic acid mesh tube (mesh pore size: approximately 10-20 ⁇ m) having a length of about 100 mm, inner diameter of about 4-5 mm and thickness of about 1 mm.
  • PGA Polyglycolic acid
  • the above collagen hydrochloric acid solution was poured into its lumen followed by freezing (-20°C x 24 hr), freeze-drying (-80°C x 48 hr under vacuum) and performing thermal dehydration crosslinking treatment (140°C x 24 hr) again.
  • the above tube having fine fibrous collagen bodies in its lumen following crosslinking treatment obtained in this manner was immersed in a PBS solution of human laminin (concentration: 10 ⁇ g/ml) followed by air-drying (this procedure was repeated three times) to obtain the artificial tube for nerve of the present invention (Type 1).
  • the artificial tube for nerve of the present invention is able to retain its shape until the nerve finishes regenerating.
  • severed nerves regenerate faster and longer in comparison with conventional artificial tubes for nerve, the state of the regenerated nerve more closely approaches the normal state, and recovery of nerve function is also favorable.
  • it can also be used as an artificial tube for spinal cord for regeneration and recovery of damaged spinal cord.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Engineering & Computer Science (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pulmonology (AREA)
  • Cardiology (AREA)
  • Biophysics (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Prostheses (AREA)
  • Materials For Medical Uses (AREA)
EP00940915A 1999-07-07 2000-07-03 Artificial neural tube Withdrawn EP1201202A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
JP19299399 1999-07-07
JP19299399 1999-07-07
PCT/JP2000/004380 WO2001003609A1 (fr) 1999-07-07 2000-07-03 Tube neural artificiel

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EP1201202A1 true EP1201202A1 (en) 2002-05-02

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EP00940915A Withdrawn EP1201202A1 (en) 1999-07-07 2000-07-03 Artificial neural tube

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EP (1) EP1201202A1 (ko)
KR (1) KR20020029069A (ko)
CN (1) CN1360484A (ko)
CA (1) CA2375595A1 (ko)
TW (1) TW512063B (ko)
WO (1) WO2001003609A1 (ko)

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EP1574229A1 (en) * 2002-12-16 2005-09-14 Gunze Limited Medical film
EP1761177A2 (en) * 2004-02-10 2007-03-14 Spinal Elements, Inc. System and method for protecting neurovascular structures
WO2007057175A2 (de) * 2005-11-17 2007-05-24 Gelita Ag Verbundmaterial, insbesondere für die medizinische anwendung, und verfahren zu dessen herstellung
DE102005054941A1 (de) * 2005-11-17 2007-05-31 Gelita Ag Nervenleitschiene
EP2347763A1 (en) * 2008-09-25 2011-07-27 Bryukhovetskiy, Andrey Stepanovich An implantable neuroendoprosthesis system, a method for preparing same and a procedure for performing of a reconstructive neurosurgical operation
CN102688076A (zh) * 2011-03-25 2012-09-26 广州迈普再生医学科技有限公司 一种神经导管及其制备方法
US8703627B2 (en) 2001-06-15 2014-04-22 Gunze Limited Antiadhesive material
US8709095B2 (en) 2006-06-30 2014-04-29 Kyoto University Thin film multilocular structure made of collagen, member for tissue regeneration containing the same, and method for producing the same
US8858597B2 (en) 2004-02-06 2014-10-14 Spinal Elements, Inc. Vertebral facet joint prosthesis and method of fixation
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USD765854S1 (en) 2011-10-26 2016-09-06 Spinal Elements, Inc. Interbody bone implant
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US9456855B2 (en) 2013-09-27 2016-10-04 Spinal Elements, Inc. Method of placing an implant between bone portions
US9820784B2 (en) 2013-03-14 2017-11-21 Spinal Elements, Inc. Apparatus for spinal fixation and methods of use
US9839450B2 (en) 2013-09-27 2017-12-12 Spinal Elements, Inc. Device and method for reinforcement of a facet
US9931142B2 (en) 2004-06-10 2018-04-03 Spinal Elements, Inc. Implant and method for facet immobilization
US10758361B2 (en) 2015-01-27 2020-09-01 Spinal Elements, Inc. Facet joint implant
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CN1360484A (zh) 2002-07-24
WO2001003609A1 (fr) 2001-01-18
CA2375595A1 (en) 2001-01-18
KR20020029069A (ko) 2002-04-17

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